title: Automated nucleotide sequencing reveals substantial disparity between the HLA-A2 genes of bone marrow transplant recipients and donors.
abstract: HLA disparity is associated with immunological complications after bone marrow transplant and it has been demonstrated that a single amino acid substitution can dramatically alter the function or allorecognition of an HLA molecule. Current serological methods for typing Class I HLA do not distinguish between most HLA-A2 variants which can differ by 1-8 amino acid residues. HLA-A2 disparity between bone marrow transplant patients and donors was investigated using automated nucleotide sequencing of the entire coding region of HLA-A2 genes. A total of 122 HLA-A2 alleles were sequenced from 47 patient-donor pairs (94 individuals). HLA-A2 disparity was observed in 10 of 47 pairs (21.3%) and consisted of HLA-A*0201 mismatched with 0202 (n = 2), 0205 (n = 3), 0206 (n = 3), 0217 (n = 1) or 0221 (n = 1). Four of 6 (66.7%) non-Caucasian or mixed race pairs were HLA-A2 disparate, while 6 of 36 (16.7%). Caucasian pairs were HLA-A2 disparate (p = 0.008). Among all individuals HLA-A*0201 was the most frequently observed allele (90.0%) while 0202 (1.6%), 0205 (2.5%), 0206 (4.1%), 0217 (0.8%) and 0221 (0.8%) were also observed. This study illustrates the diversity of HLA-A2 in non-Caucasian individuals and suggests that HLA-A2 subtyping for applications such as bone marrow transplantation, especially in non-Caucasian or mixed-race donor-recipient pairs, may be important.
authors.affiliation: University of South Carolina, Cancer Center for Treatment and Research, Columbia 29203, USA.
authors.forename: S
authors.initials: S
authors.lastname: Szmania
authors.forename: C
authors.initials: C
authors.lastname: Keever-Taylor
authors.forename: L A
authors.initials: LA
authors.lastname: Baxter-Lowe
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D016026:Bone Marrow Transplantation; D005787:Gene Frequency; D005805:Genes, MHC Class I; D015789:HLA-A2 Antigen / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D017422:Sequence Analysis, DNA
chemical_list: D015789:HLA-A2 Antigen